1. Field of the Invention
The present invention relates generally to a system and method for an improved calorimeter, and more specifically, to a system and method for an improved calorimeter for determining thermodynamic properties of chemical and biological reactions.
2. Related Art
Heat absorption and/or heat release is ubiquitous to chemical and biological reactions. Thermodynamic information that characterizes these reactions is directly measurable through calorimetry. The thermodynamic information provides insight into the molecular forces that are driving the reactions.
Conventional calorimeters used to measure chemical and biological reactions generally comprise a fluid cell and an injection syringe. The fluid cell is loaded with a liquid receptor sample. One example of a receptor sample is a protein solution. The fluid cell is then placed within a cylindrical liquid filled chamber, where temperature measurements are subsequently made.
The injection syringe is loaded with a ligand, such as a drug that binds to the receptor sample when injected into the fluid cell. A known volume of the ligand solution is then injected into the fluid cell containing the receptor sample solution. When this occurs, the ligand and receptor sample solutions bind, which causes heat to be liberated.
Thermometers, within the cylindrical liquid filled chamber, precisely measure the amount of heat released during this process. This information is recorded, and the injection and measuring steps are repeated. This process continues until heat is no longer released. This indicates that all binding sites have been filled. Once the entire process is complete, scientists can determine thermodynamic properties associated with the two interacting molecules.
That is, because the exact volumes of the samples are known, as well as the precise amount of heat liberated, scientists can determine properties such as the equilibrium binding constant, the ratio of the participating molecules in the reaction (stoichiometry), and the heat of binding. Typically, these properties are determined by constructing a binding curve comprising multiple data points that are derived from each of the reactions as described above.
The problem with conventional chemical/biological calorimeters is that the above process is very meticulous and extremely time-consuming. In addition, the sensitivity of current systems is quite limited. For example, typically current systems cannot measure dissociation binding constants below 10.sup.-8 (or affinity binding constants above 10.sup.8). It is noted that the term "binding constant" is hereinafter defined as the dissociation constant. It would be desirable to increase the sensitivity of chemical/biological calorimeters so that lower binding constants can be detected and measured.
Further, current state of the art calorimeters require relatively large sample volumes on the order of one milliliter. Using these large sample volumes can be very expensive, especially for large-scale operations, such as high-throughput pharmaceutical drug screening and the like. Still further, current systems require that solutions are more dilute as the binding constants of the systems increase.
In addition, the large sample volumes required by current calorimeters preclude the study of certain phenomena. For example, many proteins, such as transcription factors, exist in relatively small amounts in the cell. Further, amplification is not possible until a gene is cloned and an expression system is developed. Consequently, scientists are precluded from studying the thermodynamic properties of such proteins using current systems.
Accordingly, what is needed is a system and method for determining thermodynamic properties of biological and chemical reactions that can be performed using lower volumes, can detect lower binding constants, and can be performed more efficiently and economically than conventional chemical/biological calorimeter systems.